Association of growth factors with arterial recanalization and clinical outcome in patients with ischemic stroke treated with tPA: Growth factors and thrombolytic treatment

Background: Growth factors (GF) such as vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and granulocyte-colony stimulating factor (G-CSF) have been associated with greater efficacy of tissue plasminogen activator (tPA) in experimental studies. Objectives: To study the association of these GF with arterial recanalization and clinical outcome in patients with acute ischemic stroke treated with tPA. Methods: We prospectively studied 79 patients with ischemic stroke attributable to MCA occlusion treated with i.v. tPA within the first 3 h from onset of symptoms. Continuous transcranial color-coded sonography (TCCS) was performed during the first 2 h after tPA bolus to assess early MCA recanalization. Hemorrhagic transformation (HT) was classified according to ECASS II definitions. Good functional outcome was defined as a Rankin scale score of 0-2 at 90 days. GF levels were determined by ELISA. Results: Mean serum levels of VEGF, G-CSF and Ang-1 at baseline were significantly higher in patients with early MCA recanalization (n = 30) (all P < 0.0001). In the multivariate analysis, serum levels of VEGF (OR, 1.03), G-CSF (OR, 1.02) and Ang-1 (OR, 1.07) were independently associated with early MCA recanalization (all P < 0.0001). On the other hand, patients with parenchymal hematoma (PH) (n = 20) showed higher levels of Ang-1 (P < 0.0001). Ang-1 (OR, 1.12; P < 0.0001) was independently associated with PH, whereas patients with good outcome (n = 38) had higher levels of G-CSF (P < 0.0001). G-CSF was independently associated with good outcome (OR, 1.12; P = 0.036). Conclusions: These findings suggest that GF may enhance arterial recanalization in patients with ischemic stroke treated with t-PA, although they might increase the HT.